azd6244 and sorafenib in advanced hepatocellular carcinoma

Conditions: Hepatocellular Carcinoma

Summary: this will be a phase i/ii clinical trial testing the combination of sorafenib and azd6244 in advanced hepatocellular carcinoma with childs a liver cirrhosis. the aim of the phase i portion is to determine appropriate dose of this drug combination. the phase 2 study will look at effectiveness and safety of this drug combination

patients with unresectable bclc stage b/c hepatocellular carcinoma that is biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable patients without prior systemic treatment ( chemotherapy or molecular targeted therapy) except prior adjuvant therapy, if given more than 6 months ago child-pugh class a only ecog performance status 0 or 1

Eligibility criteria:
inclusion criteria: * patients with unresectable bclc stage b/c hepatocellular carcinoma that is biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable) * patients without prior systemic treatment ( chemotherapy or molecular targeted therapy) except prior adjuvant therapy, if given more than 6 months ago * patients who had prior local therapy ( tace; pei; rfa) more than 4 weeks prior to study entry * no radiotherapy within 4 weeks before entry * child-pugh class a only ( appendix a) * age 21 years and older * ecog performance status 0 or 1 ( appendix a) * life expectancy \> 3 months. * patients must have normal organ and marrow function as defined below: absolute neutrophil count \> 1.5 x 109/l;platelets\> 75 x 109/l; haemoglobin \> 9.0g/dl;total bilirubin \ 50% * measurable disease according to recist. a lesion which has previously been locally treated (including tace or rfa) is eligible as long as there is evidence of disease progression * suitable for oral administration of drug * ability to understand and the willingness to sign a written informed consent document exclusion criteria: * prior systemic therapy including sorafenib or a mek inhibitor or sunitinib or other investigational drugs * any prior local therapy ( surgery, radiation therapy, hepatic arterial embolization, or cryoablation) within 4 weeks of study entry. * prior liver transplant * nci ctcae grade \> 3 hemorrhage within 4 weeks of starting study treatment, or documented variceal hemorrhage of any grade within 12 months of study entry (as documented on endoscopy) * presence of esophageal varices (\> grade 2) at risk of bleeding and/or serious or non-healing wound/ulcer ( as documented by endoscopy) * history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study entry * patients with underlying inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea * any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism. * history of cardiac disease: * active congestive heart failure * cardiac arrythmias of nci ctcae grade \>2 or requiring pacemaker * uncontrolled hypertension * cardiomyopathy * atrial fibrillation rate \>100bpm * patients with factors that increase the risk of qt prolongation or arrhythmic events ( hypokalemia, family history of long qt interval syndrome) or qtc interval of \> 450ms for males or \> 470ms for females on screening

Keywords: hcc hepatocellular carcinoma liver cancer